【Nature】DNA活动中的交通事故风险有助于解释一些基因突变
Nature：DNA活动中的“交通事故”风险有助于解释一些基因突变
2011/02/28 14:52:18
遗传物质脱氧核糖核酸（DNA）分子拥有双链结构，在一些生命活动中，DNA分子链条就像“车道”一样，其上“行驶”着各种蛋白质。英国的一项新研究显示，在DNA分子链条中也存在较高的“交通事故”风险，相关发现有助于解释一些基因突变。
英国诺丁汉大学等机构的研究人员在新一期《自然》杂志上报告了这项成果。该校教授帕诺斯·苏尔塔纳斯说，在细胞分裂需要复制DNA时，会有一种复制体沿DNA分子链条快速运行，它相当于“快车”。而在某一段DNA分子链条中的基因需要被转录而发挥作用时，会有一种聚合酶沿相应的DNA片段运行，它的速度较慢，相当于“慢车”。
很多研究者曾一直认为，只有在复制体和聚合酶相向运行时才会“撞车”，如果它们同向运行，复制体会减慢速度跟在聚合酶后面，等聚合酶完成工作离开后再正常运行。而本次研究发现了完全不同的情况：即使在复制体和聚合酶同向运行时，也会因为两者行驶速度不同而发生大量“交通事故”。
研究人员介绍说，DNA分子中还有一种蛋白质专门负责处理这类“交通事故”，它们会把因“撞车”而“脱轨”的复制体推回正常轨道。然而，“事故”毕竟已经发生，这个过程可能导致DNA复制出现错误，或造成一些后果恶劣的基因突变，从而引发癌症等疾病。
研究人员表示，本次研究显示DNA活动中的“交通事故”风险比过去认为的要高得多，尤其是在那些基因转录频率很高的DNA片段中——也就是常有“慢车”运行的地方。因此，今后在研究基因突变时也应该重点关注这些片段的所在区域。
Nature doi:10.1038/nature09758
Co-directional replication–transcription conflicts lead to replication restart
Houra Merrikh, Cristina Machón, William H. Grainger, Alan D. Grossman & Panos Soultanas
Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability1, 2. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional. Virtually all bacteria have the highly expressed ribosomal RNA genes co-directional with replication3. In bacteria, co-directional encounters seem inevitable because the rate of replication is about 10–20-fold greater than the rate of transcription. However, these encounters are generally thought to be benign2, 4, 5, 6, 7, 8, 9. Biochemical analyses indicate that head-on encounters10 are more deleterious than co-directional encounters8 and that in both situations, replication resumes without the need for any auxiliary restart proteins, at least in vitro. Here we show that in vivo, co-directional transcription can disrupt replication, leading to the involvement of replication restart proteins. We found that highly transcribed rRNA genes are hotspots for co-directional conflicts between replication and transcription in rapidly growing Bacillus subtilis cells. We observed a transcription-dependent increase in association of the replicative helicase and replication restart proteins where head-on and co-directional conflicts occur. Our results indicate that there are co-directional conflicts between replication and transcription in vivo. Furthermore, in contrast to the findings in vitro, the replication restart machinery is involved in vivo in resolving potentially deleterious encounters due to head-on and co-directional conflicts. These conflicts probably occur in many organisms and at many chromosomal locations and help to explain the presence of important auxiliary proteins involved in replication restart and in helping to clear a path along the DNA for the replisome.